A Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib in Comparison to Placebo and With Omalizumab as Active Control in CSU Adult Patients.

Chronic Spontaneous Urticaria Clinical Trial

Official title:

A Global, Multicenter, Randomized, Double-blind, Double-dummy, Parallel-group, Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib 25 mg b.i.d. in Comparison to Placebo With Omalizumab 300 mg Every 4 Weeks as Active Control Over 52 Weeks in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by Second-generation H1-antihistamines

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06042478
• Other study ID #: CLOU064A2304
• Secondary ID: 2022-000518-32
• Status: Recruiting
• Phase: Phase 3
• Start date: November 15, 2023
• Est. completion date: March 29, 2027

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +41613241111
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to assess the efficacy, safety and tolerability of remibrutinib (LOU064) 25 milligrams (mg) twice a day (b.i.d.) over placebo for 24 weeks and in comparison to omalizumab 300 mg every 4 weeks (q4w) for 52 weeks in participants with chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines (H1-AH).

Description:

The study consists of three periods, and the total study duration is up to 72 weeks. Approximately 468 adult participants with CSU are expected to be randomized in the study.

Screening period: A screening period of up to 4 weeks will allow for the assessment of eligibility, determination of baseline disease activity and wash-out of prohibited medications.

Treatment period:

The treatment period will be double-dummy and double-blind, with placebo injections matching omalizumab 300 mg s.c. given to participants in the remibrutinib arm and placebo tablets matching remibrutinib 25 mg given to participants in the omalizumab arm (double-dummy).

At the randomization visit, eligible participants will be randomized to one of four treatment arms.

Follow-up period:

There will be a 16-week, treatment-free, safety follow-up period (for participants who do not roll-over to the extension study).

All participants will be on a stable, local label-approved standard dose of a second-generation H1-AH ("background therapy") throughout the entire study (starting a minimum of 7 days prior to randomization until the end of the study). In addition, to treat unbearable symptoms of CSU flare-ups, participants will be allowed to use a different second-generation H1-AH on an as-needed basis ("rescue therapy").

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 468
• Est. completion date: March 29, 2027
• Est. primary completion date: August 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female adult participants =18 years of age at the time of signing the informed consent.

• CSU duration for = 6 months prior to screening.

• Diagnosis of CSU inadequately controlled by second generation H1-AH at the time of randomization, defined as:

• The presence of itch and hives for =6 consecutive weeks prior to screening, despite the use of second-generation H1-AH during this time period.

• UAS7 score (range 0-42) =16, ISS7 score (range 0-21) = 6 and HSS7 score (range 0- 21) = 6 during the 7 days prior to randomization (Day 1).

• Documentation of hives within three months before randomization.

• Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol.

• Participants must not have had more than one missing UPDD entry (either morning or evening) in the 7 days prior to randomization (Day 1).

Exclusion Criteria:

• Prior exposure to ligelizumab, omalizumab and other biologics with any effect in CSU, including anti-IgE therapies.

• Significant bleeding risk or coagulation disorders.

• History of gastrointestinal bleeding.

• Requirement for anti-platelet or anti-coagulant medication.

• History or current hepatic disease.

• Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant.

• Evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines.

• Documented history of anaphylaxis.

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• Remibrutinib
Active treatment
• Placebo to remibrutinib
Placebo followed by active treatment
• Placebo to omalizumab
Placebo followed by active comparator
• Omalizumab
Active comparator

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Bahia Blanca
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Capital Federal
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Woolloongabba	Queensland
Brazil	Novartis Investigative Site	Alphaville Barueri	Sao Paulo
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Santo Andre	SP
Brazil	Novartis Investigative Site	Sorocaba	SP
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Niagara Falls	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Verdun	Quebec
Czechia	Novartis Investigative Site	Brno	Czech Republic
Czechia	Novartis Investigative Site	Plzen Bolevec
Czechia	Novartis Investigative Site	Prague 10
France	Novartis Investigative Site	Bobigny Cedex
France	Novartis Investigative Site	La Rochelle
France	Novartis Investigative Site	La Tronche
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Pierre Benite
France	Novartis Investigative Site	Rouen
France	Novartis Investigative Site	Toulon Cedex 9	Val De Marne
Germany	Novartis Investigative Site	Bad Bentheim
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Luebeck
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Osnabrueck
Germany	Novartis Investigative Site	Stade
Germany	Novartis Investigative Site	Tuebingen
Hungary	Novartis Investigative Site	Kaposvar
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Belagavi	Karnataka
India	Novartis Investigative Site	Bikaner	Rajasthan
India	Novartis Investigative Site	DehraDun	Uttarakhand
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Mysore	Karnataka
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	New Delhi
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Roma
Italy	Novartis Investigative Site	Rozzano	MI
Korea, Republic of	Novartis Investigative Site	Ansan	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Seoul
Malaysia	Novartis Investigative Site	Ipoh	Perak
Malaysia	Novartis Investigative Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Novartis Investigative Site	Muar	Johor
Malaysia	Novartis Investigative Site	Penang
Malaysia	Novartis Investigative Site	Petaling Jaya	Selangor Darul Ehsan
Malaysia	Novartis Investigative Site	Wilayah Persekutuan
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Utrecht
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Krosno
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Warszawa
Slovakia	Novartis Investigative Site	Bardejov
Slovakia	Novartis Investigative Site	Kezmarok
Slovakia	Novartis Investigative Site	Svidnik
Slovakia	Novartis Investigative Site	Trnava
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	Granada	Andalucia
Spain	Novartis Investigative Site	Las Palmas de Gran Canaria
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Pozuelo de Alarcon	Madrid
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Geneve
Switzerland	Novartis Investigative Site	St Gallen
Switzerland	Novartis Investigative Site	Zuerich
Switzerland	Novartis Investigative Site	Zuerich
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
Thailand	Novartis Investigative Site	Bangkok	Phayathai
Thailand	Novartis Investigative Site	Bangkoknoi	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen	THA
Thailand	Novartis Investigative Site	Songkhla	Hat Yai
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Denizli
Turkey	Novartis Investigative Site	Fatih / Istanbul
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Sakarya

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Hungary,  India,  Italy,  Korea, Republic of,  Malaysia,  Netherlands,  Poland,  Slovakia,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute change from baseline in Weekly Urticaria Activity Score (UAS7)	The UAS7 is the sum of the Weekly Hives Severity Score (HSS7 score) and the Weekly Itch Severity Score (ISS7 score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).	Week 12
Secondary	Achievement of UAS7=0 (yes/no)	Complete UAS7 response is UAS7 = 0	Week 12
Secondary	Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score	The severity of the itch will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.	Week 12
Secondary	Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score	The hives (wheals) severity score, defined by number of hives, will be recorded by the participant twice daily in their eDiary, on a scale of 0 (none) to 3 (> 12 hives/12 hours). A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.	Week 12
Secondary	Occurrence of treatment-emergent adverse events and serious adverse events (SAEs)	To demonstrate the safety and tolerability of remibrutinib (25 mg b.i.d.)	up to 68 weeks